Hepatitis C virus core protein transactivates the inducible nitric oxide synthase promoter via NF-κB activation

Lucas, Susana de; Bartolomé, Javier; Amaro, Maria José; Carréño, Vicente

doi:10.1016/j.antiviral.2003.08.006

Cited by 24 publications

(16 citation statements)

References 37 publications

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“…Indeed, a parallel decrease in the NADPH level is most consistent with an increased consumption of GSH, as NADPH participates in a reaction that recycles GSSG back to GSH. In addition, core protein has also been shown to modulate the production of cytokines and host enzymes that can increase ROS/RNS, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [67][68][69][70][71][72][73]. These observations are consistent with the fact that HCV core protein, in addition to forming viral capsid, has many other functions in the modulation of host cell functions and pathogenesis [74][75][76].…”

Section: Redox Regulation Of Hepatitis C Virus In the Pathogenesisupporting

confidence: 73%

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Seronello

Sheikh²,

Choi

2007

Free Radical Biology and Medicine

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Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family that is estimated to have infected 170 million people worldwide. HCV can cause serious liver disease in humans such as cirrhosis, steatosis, and hepatocellular carcinoma. HCV induces a state of oxidative/nitrosative stress in patients through multiple mechanisms, and this redox perturbation has been recognized as a key player in the HCV-induced pathogenesis. Studies have shown that alcohol synergizes with HCV in the pathogenesis of liver disease, and part of these effects may be mediated by reactive species that are generated during hepatic metabolism of alcohol. Furthermore, reactive species and alcohol may influence HCV replication and the outcome of interferon therapy. Alcohol consumption has also been associated with increased sequence heterogeneity of the HCV RNA sequences, suggesting multiple modes of interaction between alcohol and HCV.This review summarizes current understanding of oxidative and nitrosative stress during HCV infection and possible combined effects of HCV, alcohol, and reactive species in the pathogenesis of liver disease.

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Section: Redox Regulation Of Hepatitis C Virus In the Pathogenesisupporting

confidence: 73%

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Seronello

Sheikh²,

Choi

2007

Free Radical Biology and Medicine

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“…The plasmids pHCV-Co, in which the complete coding region of HCV-Co protein (1b genotype) was cloned in the plasmid pCI (Promega) under the control of cytomegalovirus immediate early promoter, and pMx4CAT, in which chloramphenycol acethyl transferase (CAT) gene was cloned under the control of a 969-bp fragment of the MxA gene promoter containing 3 ISRE sequences, have been described elsewhere [25,26]. The irrelevant plasmid pGEM3Z (Promega) was also used.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis C Virus Core Protein Down‐Regulates Transcription of Interferon‐Induced Antiviral Genes

2005

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“…HCV core gene expression diminishes the intracellular GSH levels and the mitochondrial NADPH content that are associated with increased uptake of calcium and oxidative stress generation at complex I in mitochondria, providing an action mechanism for HCVinduced ROS production [42,91,92,96]. On the contrary, core protein modulates the production of cytokines and host enzymes, such as cyclooxygenase-2 and inducible nitric oxide synthase (iNOS), which can increase ROS and RNS [97][98][99][100][101][102][103].…”

Section: Viral Hepatitis and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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Hepatitis C virus core protein transactivates the inducible nitric oxide synthase promoter via NF-κB activation

Cited by 24 publications

References 37 publications

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Hepatitis C Virus Core Protein Down‐Regulates Transcription of Interferon‐Induced Antiviral Genes

Role of free radicals in liver diseases

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